Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment
Published by Elsevier Inc..
The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.
| Errataetall: |
CommentIn: Cell. 2021 Oct 14;184(21):5301-5303. - PMID 34624223 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:184 |
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| Enthalten in: |
Cell - 184(2021), 21 vom: 14. Okt., Seite 5338-5356.e21 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lam, Khiem C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.01.2022 Date Revised 26.02.2024 published: Print-Electronic CommentIn: Cell. 2021 Oct 14;184(21):5301-5303. - PMID 34624223 Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2021.09.019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331651858 |
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| 245 | 1 | 0 | |a Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment |
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| 500 | |a Date Completed 03.01.2022 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Cell. 2021 Oct 14;184(21):5301-5303. - PMID 34624223 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Elsevier Inc. | ||
| 520 | |a The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a STING | |
| 650 | 4 | |a cancer immunology | |
| 650 | 4 | |a dendritic cells | |
| 650 | 4 | |a immune checkpoint blockade immunotherapy | |
| 650 | 4 | |a innate immunity | |
| 650 | 4 | |a interferon | |
| 650 | 4 | |a macrophages | |
| 650 | 4 | |a microbiota | |
| 650 | 4 | |a monocytes | |
| 650 | 4 | |a tumor microenvironment | |
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| 650 | 7 | |a Sting1 protein, mouse |2 NLM | |
| 650 | 7 | |a cyclic diadenosine phosphate |2 NLM | |
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| 700 | 1 | |a Huang, April |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Quanyi |e verfasserin |4 aut | |
| 700 | 1 | |a Di Modica, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Richard R |e verfasserin |4 aut | |
| 700 | 1 | |a Lopès, Amélie |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Sarah B |e verfasserin |4 aut | |
| 700 | 1 | |a Schwarz, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Bohrnsen, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Cogdill, Alexandria P |e verfasserin |4 aut | |
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| 700 | 1 | |a Lee, Maxwell P |e verfasserin |4 aut | |
| 700 | 1 | |a Goldszmid, Romina S |e verfasserin |4 aut | |
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